Implications of gut microbiota dysbiosis and metabolic changes in prion disease

Yang, Dongming; Zhao, Deming; Shah, Syed Qaiser; Wu, Wei; Lai, Mengyu; Zhang, Xixi; Li, Jie; Guan, Zhiling; Zhao, Huafen; Li, Wen; Gao, Hong-Li; Zhou, Xiangmei; Yang, Lifeng

doi:10.1016/j.nbd.2019.104704

Cited by 36 publications

(27 citation statements)

References 51 publications

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“…Concentrations of SCFAs in cecal contents and serum were measured by GC-MS as described previously ( 26 ). Briefly, 800-μL sample aliquots were filtered, and the protein-free filtrate was stored at −20°C before vacuum distillation.…”

Section: Methodsmentioning

confidence: 99%

Alterations in the Gut Microbiome and Cecal Metabolome During Klebsiella pneumoniae-Induced Pneumosepsis

et al. 2020

Front. Immunol.

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Klebsiella (K.) pneumoniae is a common cause of pneumonia-derived sepsis in human and is associated with high morbidity and mortality. The microbiota promotes and maintains host immune homeostasis during bacterial infections. However, the mechanisms by which the gut microbiota affects immune responses in the lung still remain poorly understood. Here, we performed cecal metabolomics sequencing and fecal 16s rRNA sequencing in K. pneumoniae-infected mice and uninfected controls and showed that K. pneumoniae infection led to profound alterations in the gut microbiome and thus the cecal metabolome. We observed that the levels of Lactobacillus reuteri and Bifidobacterium pseudolongum were significantly decreased in K. pneumoniae-infected mice. Spearman correlation analysis showed that alterations in the richness and composition of the gut microbiota were associated with profound changes in host metabolite concentrations. Further, short-chain fatty acids (SCFAs), including acetate, propionate, and butyrate, were detected in cecal contents and serum by gas chromatography-mass spectrometry (GC-MS). We observed that the concentrations of these three SCFAs were all lower in the infected groups than in the untreated controls. Lastly, oral supplementation with these three SCFAs reduced susceptibility to K. pneumoniae infections, as indicated by lower bacterial burdens in the lung and higher survival rates. Our data highlight the protective roles of gut microbiota and certain metabolites in K. pneumoniae-pneumonia and suggests that it is possible to intervene in this bacterial pneumonia by targeting the gut microbiota.

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Section: Methodsmentioning

confidence: 99%

Alterations in the Gut Microbiome and Cecal Metabolome During Klebsiella pneumoniae-Induced Pneumosepsis

et al. 2020

Front. Immunol.

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“…Interestingly, these same elements are considered among the factors that can have a strong impact on the balance between beneficial and harmful microbes that inhabit the gut, which represent the consortium of approximately 10 14 –10 15 bacteria present in the gut microbiota [ 95 , 96 , 97 ]. In fact, even if the gut microbiota has been defined by some authors as “the forgotten organ” [ 98 ], in recent years it has regained its spotlight, as it can orchestrate a wide range of physiological functions, well beyond the intestinal one: from metabolism [ 99 ], neurogenesis [ 100 ], protection against pathogens [ 101 ], to development and regulation of host immunity and the preservation of the integrity of the intestinal barrier [ 102 ].…”

Section: Co-factors Involved In the Misfolding Processmentioning

confidence: 99%

“…Interestingly, a recent study in an animal model of prion disease reported similar alterations in the gut microbiota with an overgrow of Proteobacteria and a decrease in Prevotellaceae, associated with a reduction in SCFAs concentration [ 98 ]. Several studies have suggested that exposure to commensal bacteria and bacteria components, particularly LPS, may promote LPS-prion protein interaction [ 132 ], causing an overexpression of normal PrP C in the gut mucosa [ 133 ], which could trigger its conversion into aggregate forms.…”

Section: Co-factors Involved In the Misfolding Processmentioning

confidence: 99%

Parkinson’s Disease: A Prionopathy?

Vascellari,

Manzin

2021

IJMS

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The principal pathogenic event in Parkinson’s disease is characterized by the conformational change of α-synuclein, which form pathological aggregates of misfolded proteins, and then accumulate in intraneuronal inclusions causing dopaminergic neuronal loss in specific brain regions. Over the last few years, a revolutionary theory has correlated Parkinson’s disease and other neurological disorders with a shared mechanism, which determines α-synuclein aggregates and progresses in the host in a prion-like manner. In this review, the main characteristics shared between α-synuclein and prion protein are compared and the cofactors that influence the remodeling of native protein structures and pathogenetic mechanisms underlying neurodegeneration are discussed.

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“…27 Considerando los mecanismos fisiopatológicos descritos, Yang D y colaboradores describen una probable relación de la microbiota con el acceso al cerebro y la replicación temprana intestinal de las proteínas implicadas en la enfermedad por priones. 28…”

Section: Eje Microbiota-intestino-cerebrounclassified

Microbiota intestinal: el órgano olvidado

Rivera¹,

Pacheco²,

Greene³

et al. 2021

Acta Médica Grupo Ángeles

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En los últimos 10 años, se han publicado diversos artículos relacionados con la microbiota humana, especialmente la intestinal. Este ecosistema de microorganismos, en su conjunto resguarda un genoma más amplio que el del ser humano, lo cual le confiere capacidad de regular procesos que convergen en la fisiología de diversas vías inmunológicas y en la fisiopatología de enfermedades intestinales y extraintestinales. Aplicar estos nuevos conceptos en la evaluación clínica, paraclínica y terapéutica de un paciente hoy en día representa un reto, ya que los factores implicados en la formación de la microbiota, en los cambios que presenta a lo largo de la vida y los factores que influyen en alterar y mantener su composición, diversidad y metabolismo, son muy variables. Algunos fuera de nuestro control como el tipo de nacimiento, pero otros como la dieta, consumo de fibra y probióticos, interfieren de manera importante con modificaciones a la microbiota y posteriormente a la salud en general del huésped. La siguiente revisión consiste en una síntesis de los aspectos funcionales más relevantes de la microbiota intestinal, esto con el objetivo de difundir el tema y motivar a nuevas investigaciones enfocadas a aplicaciones clínico-terapéuticas.

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Implications of gut microbiota dysbiosis and metabolic changes in prion disease

Cited by 36 publications

References 51 publications

Alterations in the Gut Microbiome and Cecal Metabolome During Klebsiella pneumoniae-Induced Pneumosepsis

Alterations in the Gut Microbiome and Cecal Metabolome During Klebsiella pneumoniae-Induced Pneumosepsis

Parkinson’s Disease: A Prionopathy?

Microbiota intestinal: el órgano olvidado

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